The Studies On The Hydration Of Nitriles To Amides And Copper-Catalyzed C-N Coupling Reaction Of Amides

Amides are one of the most important compounds, which are widely used in the field of engineering plastics, fragrances, inks, detergents, etc. Most of substituted aromatic amides have biological activity. Particularly, the compounds of N-pyrimidine amine phenyl substituted amides have the effect of anti-cancer and anti-inflammation. Among them, the imatinib was used in the treatment of chronic spinal leukemia. The method of more simple and feasible was found by us, which was achieved hydration of aromatic nitriles to aromatic amides. Then, the copper catalyst was used in C-N coupling reaction, achieved aromatic amides react with bromophenyl pyrimidinamine to produce compounds of N-pyrimidine amino phenyl substituted amides.The study was took sodium aluminate (NaAlO) as a catalyst by us, the successful conversion of aromatic nitriles into aromatic amides in the solvent of the water-alcohol system. This method is a highly selective reaction, overcome excessive hydrolysis and the product was easy to separate. The effects of reaction temperature and reaction time, a number of catalysts, were examined on the yields of the hydration reaction. The optimized condition is 25mol% NaAlO2, in the water-ethanol mixed solvent under 70 ℃, at 6 hours. The yield of Aromatic amides is 75-93%.For copper-catalyzed C-N coupling reaction of amides, the novel method has achieved the reaction in the water-toluene system without isolated from the air. The type of solvent and base, the proportion of water and toluene were optimized.20mol% CuI,10mol% N.N’-dimethylethylenediamine (DMEDA) and 200mol% of K2CO3 was employed, and added 10mol% D-sodium ascorbate (D-NaAsc) to provide for the protection, the feed ratio of Bromophenyl pyrimidinamine with amide were the amount of substance ratio of 1.2:1, as well as under the reflux temperature to well stir for 24h in toluene. Eventually this condition was synthesized six kinds of pyridylcarboximides. The compounds of N-pyrimidine amino phenyl substituted amides in yield of 36%-81%.Above all, in this study.21 kinds of organic compounds were synthesized. In which we adopted two mild methods,9 kinds of aromatic form amides were successfully synthesized,7 kinds of compounds of N-pyrimidine amino phenyl substituted amides were achieved, which have potential anti-cancer activity. The Synthetic products have greater development space in the field of pharmaceutical synthesis.